Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort

Annette T Hastie; Fernando J Martinez; Jeffrey L Curtis; Claire M Doerschuk; Nadia N Hansel; Stephanie Christenson; Nirupama Putcha; Victor E Ortega; R Graham Barr; Xingnan Li; Elizabeth E Carretta; David J Couper; Christopher B Cooper; Eric A Hoffman; Richard E Kanner; Eric Kleerup; Wanda K O'Neal; Robert Paine III; Stephen P Peters; Neil E Alexis; Prescott G Woodruff; MeiLan K Han; Deborah A Meyers; Eugene R Bleecker

doi:10.1016/S2213-2600(17)30432-0

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Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort

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Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort

Annette T Hastie, Fernando J Martinez, Jeffrey L Curtis, Claire M Doerschuk, Nadia N Hansel, Stephanie Christenson, Nirupama Putcha, Victor E Ortega, R Graham Barr, Xingnan Li, …

The lancet respiratory medicine, Vol.5(12), pp.956-967

12/2017

DOI: 10.1016/S2213-2600(17)30432-0

PMCID: PMC5849066

PMID: 29146301

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Abstract

Increased concentrations of eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with increased frequency of exacerbations, reduced lung function, and corticosteroid responsiveness. We aimed to assess whether high eosinophil concentrations in either sputum or blood are associated with a severe COPD phenotype, including greater exacerbation frequency, and whether blood eosinophils are predictive of sputum eosinophils. We did a multicentre observational study analysing comprehensive baseline data from SPIROMICS in patients with COPD aged 40-80 years who had a smoking history of at least 20 pack-years, recruited from six clinical sites and additional subsites in the USA between Nov 12, 2010, and April 21, 2015. Inclusion criteria for this analysis were SPIROMICS baseline visit data with complete blood cell counts and, in a subset, acceptable sputum counts. We stratified patients on the basis of blood and sputum eosinophil concentrations and compared their demographic characteristics, as well as results from questionnaires, clinical assessments, and quantitative CT (QCT). We also analysed whether blood eosinophil concentrations reliably predicted sputum eosinophil concentrations. This study is registered with ClinicalTrials.gov (NCT01969344). Of the 2737 patients recruited to SPIROMICS, 2499 patients were smokers and had available blood counts, and so were stratified by mean blood eosinophil count: 1262 patients with low (<200 cells per μL) and 1237 with high (≥200 cells per μL) blood eosinophil counts. 827 patients were eligible for stratification by mean sputum eosinophil percentage: 656 with low (<1·25%) and 171 with high (≥1·25%) sputum eosinophil percentages. The high sputum eosinophil group had significantly lower median FEV percentage predicted than the low sputum eosinophil group both before (65·7% [IQR 51·8-81·3] vs 75·7% [59·3-90·2], p<0·0001) and after (77·3% [63·1-88·5] vs 82·9% [67·8-95·9], p=0·001) bronchodilation. QCT density measures for emphysema and air trapping were significantly higher in the high sputum eosinophil group than the low sputum eosinophil group. Exacerbations requiring corticosteroids treatment were more common in the high versus low sputum eosinophil group (p=0·002). FEV percentage predicted was significantly different between low and high blood eosinophil groups, but differences were less than those observed between the sputum groups. The high blood eosinophil group had slightly increased airway wall thickness (0·02 mm difference, p=0·032), higher St George Respiratory Questionnaire symptom scores (p=0·037), and increased wheezing (p=0·018), but no evidence of an association with COPD exacerbations (p=0·35) or the other indices of COPD severity, such as emphysema measured by CT density, COPD assessment test scores, Body-mass index, airflow Obstruction, Dyspnea, and Exercise index, or Global Initiative for Chronic Obstructive Lung Disease stage. Blood eosinophil counts showed a weak but significant association with sputum eosinophil counts (receiver operating characteristic area under the curve of 0·64, p<0·0001), but with a high false-discovery rate of 72%. In a large, well characterised cohort of former and current smoking patients with a broad range of COPD severity, high concentrations of sputum eosinophils were a better biomarker than high concentrations of blood eosinophils to identify a patient subgroup with more severe disease, more frequent exacerbations, and increased emphysema by QCT. Blood eosinophils alone were not a reliable biomarker for COPD severity or exacerbations, or for sputum eosinophils. Clinical trials targeting eosinophilic inflammation in COPD should consider assessing sputum eosinophils. National Institutes of Health, and National Heart, Lung, and Blood Institute.

Bronchodilator Agents - therapeutic use

Severity of Illness Index

Sputum - cytology

Humans

Middle Aged

Male

Lung - physiopathology

Biomarkers - blood

Forced Expiratory Volume

Adrenal Cortex Hormones - adverse effects

Sputum - immunology

Pulmonary Disease, Chronic Obstructive - blood

Female

ROC Curve

Aged

Leukocyte Count

Eosinophils

Pulmonary Disease, Chronic Obstructive - drug therapy

Details

Title: Subtitle: Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort
Creators: Annette T Hastie - Wake Forest School of Medicine, Winston-Salem, NC, USA. Electronic address: ahastie@wakehealth.edu
Fernando J Martinez - Weill Cornell Medical College of Cornell University, New York, NY, USA
Jeffrey L Curtis - VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; University of Michigan, Ann Arbor, MI, USA
Claire M Doerschuk - University of North Carolina School of Medicine, Chapel Hill, NC, USA
Nadia N Hansel - Johns Hopkins University, Baltimore, MD, USA
Stephanie Christenson - University of California San Francisco, San Francisco, CA, USA
Nirupama Putcha - Johns Hopkins University, Baltimore, MD, USA
Victor E Ortega - Wake Forest School of Medicine, Winston-Salem, NC, USA
R Graham Barr - Columbia University/Presbyterian Hospital, New York, NY, USA
Xingnan Li - University of Arizona College of Medicine, Tucson, AZ, USA
Elizabeth E Carretta - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
David J Couper - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Christopher B Cooper - David Geffen School of Medicine, Los Angeles, CA, USA
Eric A Hoffman - University of Iowa, Iowa City, IA, USA
Richard E Kanner - University of Utah Health Sciences Center, Salt Lake City, UT, USA
Eric Kleerup - David Geffen School of Medicine, Los Angeles, CA, USA
Wanda K O'Neal - University of North Carolina School of Medicine, Chapel Hill, NC, USA
Robert Paine III - University of Utah Health Sciences Center, Salt Lake City, UT, USA; Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA
Stephen P Peters - Wake Forest School of Medicine, Winston-Salem, NC, USA
Neil E Alexis - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Prescott G Woodruff - University of California San Francisco, San Francisco, CA, USA
MeiLan K Han - University of Michigan, Ann Arbor, MI, USA
Deborah A Meyers - University of Arizona College of Medicine, Tucson, AZ, USA
Eugene R Bleecker - University of Arizona College of Medicine, Tucson, AZ, USA
Resource Type: Journal article
Publication Details: The lancet respiratory medicine, Vol.5(12), pp.956-967
DOI: 10.1016/S2213-2600(17)30432-0
PMID: 29146301
PMCID: PMC5849066
NLM abbreviation: Lancet Respir Med
ISSN: 2213-2600
eISSN: 2213-2619
Publisher: England
Grant note: HHSN268200900017C / NHLBI NIH HHS P30 ES005605 / NIEHS NIH HHS HHSN268200900019C / NHLBI NIH HHS HHSN268200900020C / NHLBI NIH HHS U01 HL137880 / NHLBI NIH HHS HHSN268200900015C / NHLBI NIH HHS I01 CX000911 / CSRD VA HHSN268200900013C / NHLBI NIH HHS HHSN268200900016C / NHLBI NIH HHS HHSN268200900018C / NHLBI NIH HHS HHSN268200900014C / NHLBI NIH HHS K23 HL130627 / NHLBI NIH HHS K23 HL123594 / NHLBI NIH HHS
Language: English
Date published: 12/2017
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
Record Identifier: 9984051571802771

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